Richard Whale

Pindolol augmentation of serotonin reuptake inhibitors for the treatment of depressive disorder: a systematic review.

Adding pindolol to serotonergic antidepressant treatment offers a potential strategy for producing a more rapid onset of action and an enhanced antidepressant effect. This review investigated whether pindolol enhances the efficacy of serotonergic antidepressant treatment in adult patients with depressive disorders at sequential time points up to 6 weeks. Search strategy: Cochrane Collaboration Depression, Anxiety and Neurosis-Controlled Trials Register plus unpublished trial data. Study selection: Randomised trials including depressed patients, comparing serotonergic antidepressants + pindolol with serotonergic antidepressants + placebo and using depressive symptom clinical outcomes scales. Data extraction: Clinical response at time points up to 6 weeks as defined by >50% depression scale score reduction was extracted for each trial as possible. Eleven studies were identified including unpublished data. The pooled odds ratios for dichotomous response to treatment at time points from 1 to 6 weeks were 2.39 (95% CI 1.40—4.06), 2.39 (1.74—3.29), 1.94 (1.46—2.58), 1.59 (1.16—2.18), 1.42 (0.87—2.31) and 1.28 (0.91—1.81). Time-to-event analysis showed a greater response with pindolol augmentation versus placebo (P = 0.04). There was significant heterogeneity between studies at some time points. Dropout rates did not significantly differ between treatment arms. This review suggests an overall beneficial clinical effect of pindolol augmentation, most clearly up to 4 weeks of treatment.

Effectiveness and predictors of continuation of paliperidone palmitate long-acting injection treatment: a 12-month naturalistic cohort study

Abstract Antipsychotic long-acting injectable (LAI) medication has an important place as a treatment option in schizophrenia with evolving evidence to support clinical benefit over oral medication. Paliperidone palmitate is recently licensed as an LAI. We studied a naturalistic cohort of all identifiable patients who initiated paliperidone LAI in a specific United Kingdom region (Sussex) from first availability up to January 2013 (n = 179). Favorably, 60% of the cohort continued paliperidone LAI beyond 12 months from initiation. Schizophrenia diagnosis was significantly associated with 12-month continuation on univariate analysis (65% continuation rate at 12 months in this diagnostic subgroup). No baseline variables were identified as independently associated with 12-month continuation. However, fewer inpatient days after initiation (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003–1.011; P = 0.002), dose adjustment up or down (OR, 3.46; 95% CI, 1.26–9.51; P = 0.016), and a higher maintenance dose (OR, 8.31; 95% CI, 1.84–37.51; P = 0.006) during treatment course were all independently associated with continuation on multivariate analysis. Our findings support the importance of a collaborative approach with the LAI recipient in treatment decision making to enhance treatment effectiveness.

Pre-treatment waking cortisol response and vulnerability to interferon α induced depression

Depressive disorder is a common consequence of interferon α treatment. An understanding of the aetiological processes involved is evolving. HPA axis abnormalities are clearly described in community depressive disorder and represent vulnerability to depression development. We explored whether pre-treatment HPA axis abnormalities influence depression emergence during interferon α treatment. We examined waking HPA axis response via salivary cortisol sampling in 44 non-depressed, chronic hepatitis C infected patients due to commence standard interferon α treatment. Hamilton depression scales and the structured clinical interview for DSM-IV major depressive disorder status were administered monthly during treatment. Major depressive disorder developed in 26 of 44 subjects during interferon-α treatment. The pre-treatment waking cortisol response over 1h was significantly greater in the subsequent switch to depression group (F=4.23, p=0.046). The waking cortisol response pre-treatment with interferon α appears greater in those subsequently switching to depressive disorder during treatment. This waking response may join other vulnerability factors for depression emergence in this group. This model could prove a valuable tool in understanding non-iatrogenic depressive disorder in the general population and notably the role of cytokines.

Effectiveness of antipsychotics used in first-episode psychosis: a naturalistic cohort study.

Background One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP). Aims To investigate the effectiveness of commonly used antipsychotic medications in FEP. Method A retrospective cohort study of naturalistic treatment of patients (N=460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files. Results Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation. Conclusions Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus. Declaration of interest R.W., A.T. and S.M. have received research grant, speaker honoraria and conference attendance funding from all companies marketing antipsychotics. Copyright and usage

Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis

ABSTRACT Cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono-infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis also indicated that HIV mono-infected patients had a significantly lower global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of included studies, heterogeneity of the samples and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections.

Psychomotor retardation and vulnerability to interferon alpha induced major depressive disorder: Prospective study of a chronic hepatitis C cohort

BACKGROUND Major depressive disorder (MDD) is a common consequence of interferon alpha (IFNα) treatment and important supporting evidence of a role of inflammation in the aetiology of depression. OBJECTIVE This study aimed to expand the knowledge of baseline clinical vulnerability characteristics to IFNα induced MDD, particularly exploring sub-threshold depressive symptoms. METHODS A prospective cohort of chronic HCV patients undergoing treatment with pegylated-IFNα and ribavirin was studied. MDD was assessed using the Structured Clinical Interview for DSM-IV (SCID-I). Depressive symptoms and severity were assessed at baseline and monthly with the Hamilton Depression Rating Scale (HAMD). Subjects with MDD or taking antidepressant treatment at baseline were excluded. RESULTS 278 patients were assessed for this cohort with a final study sample of 190. 94.2% had contracted HCV through intravenous drug use. During six months IFNα treatment, 53.2% of patients transitioned to DSM-IV threshold MDD. In the multivariate logistic analysis, independent factors significantly associated with development of MDD were younger age (OR 0.96, 95% CI 0.93-1.00, p=0.028), past history of MDD (OR 3.82, 95% CI 1.63-8.92, p=0.002), baseline HAMD items psychomotor retardation (OR 15.21, 95% CI 1.33-173.41, p=0.032) and somatic symptoms (general) (OR 2.96, 95% CI 1.44-6.08, p=0.003), and HCV genotype 2 (OR 2.27, 95% CI 1.07-4.78, p=0.032). CONCLUSIONS During IFNα treatment, the rate of transition to MDD was high in this cohort. Psychomotor retardation and somatic symptoms may represent a greater inflamed state pre-treatment. This iatrogenic model of MDD may offer important insights into wider depression aetiology.

The access and waiting-time standard for first-episode psychosis: an opportunity for identification and treatment of psychosis risk states?

Expansion of early intervention services to identify and clinically manage at-risk mental state for psychosis has been recently commissioned by NHS England. Although this is a welcome development for preventive psychiatry, further clarity is required on thresholds for definition of such risk states and their ability to predict subsequent outcomes. Intervention studies for these risk states have demonstrated that a variety of interventions, including those with fewer adverse effects than antipsychotic medication, may potentially be effective but they should be interpreted with caution.

HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder.

Hepatitis C (HCV) treatment options have changed with the development of direct activity antivirals (DAAs) and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated‐interferon and ribavirin treatment is major depressive disorder (MDD), however little is known about such adverse events with protease inhibitor‐based triple therapy. The aim of this study was to assess the rate of MDD in co‐infected HIV HCV patients undergoing different HCV treatments.

Depression in HIV and HCV co-infected patients: a systematic review and meta-analysis

Abstract The aim of this study was to carry out a systematic review and meta-analysis of the differences in the prevalence of depression and presence of depressive symptoms between HIV/HCV co-infection, HIV mono-infection, and hepatitis C virus (HCV) mono-infection. A systematic electronic search of bibliographic databases was performed to locate articles published from the earliest available online until December 2014. Outcomes of depression were based on clinical interviews and validated self-reported measures of depression/depressive symptoms. Of the 188 records initially screened, 29 articles were included in the descriptive systematic review and six were included in the meta-analysis. The meta-analytic results indicated that, as measured by self-reported measures of depression, HIV/HCV co-infected patients were significantly more likely to report depressive symptoms than either HIV (SMD = .24, 95% CI: .03–.46, p = .02) or HCV mono-infected (SMD = .55, 95% CI: .17–.94, p = .005) patients. The variability of the results of the reviewed studies, largely dependent on the samples’ characteristics and the methods of assessment of depression, suggests that a clear interpretation of how depression outcomes are affected by the presence of HIV/HCV co-infection is still needed. Failing to diagnose depression or to early screen depressive symptoms may have a significant impact on patients’ overall functioning and compromise treatments’ outcomes.

Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C

In this prospective study, we examined new-onset major depressive disorder (MDD) and the differential expression of depressive symptoms in a sample of 132 HCV mono-infected and 40 HIV/HCV co-infected patients initiating pegylated interferon-based treatment, including protease inhibitor therapy. The semi-structured clinical interview (SCID-I) was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Of the total sample, 60 patients (34.9%) developed SCID-I defined MDD during antiviral treatment. The proportion of HCV mono- and HIV/HCV patients developing MDD during treatment was not significantly different (37.9% vs. 25%; p=0.185). In both groups, there was a significant increase in HAMD total score from baseline to week 4, and a significant decrease between week 24 and 6 months post-treatment cessation. The greatest increase was observed in the symptoms of the neurovegetative syndrome. HCV mono-infected patients reported higher scores than co-infected patients, particularly impaired activity and somatic symptoms, but the differences were only significant at week 12. The finding that co-infected patients appear less vulnerable to the development of depressive symptoms during HCV treatment than HCV mono-infected patients warrants further exploration, including a thorough analysis of the biological and psychosocial factors associated with this emergence.